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organelle identity

As cargos move through the endocytic pathway the organelles within which they reside undergo a maturation process. The lumen acidifies, phosphoinositide lipids on the organelle membrane are remodeled, and proteins that mark the early endosome are selectively removed while proteins characteristic of later ensodomes and lysosomes are added to the organelle through fusion events. At the same time a remarkable morphological transition is sequestering cargos into intraluminal vesicles (ILVs) to form the multivesicular body (MVB).

A key transition in this elaborate dance occurs when the late endosome ceases to accept inbound traffic from the plasma membrane and Golgi (processes dependent on small G proteins of the Rab5 family), and becomes competent to fuse with the terminal lysosomal compartment (an event controlled by Rab7). The transition from Rab5 to Rab7 signaling is clearly related to the formation of the MVB morphology, but the specific signals that trigger the Rab5-to-Rab7 transition are poorly understood.

Recently, we have identified key enzymes and other regulators that control the signaling state of Rab5 and Rab7. At the same time our collaborators in the Odorizzi group at the University of Colorado, Boulder have made substantial process in linking molecules that drive MVB formation to the Rab5-Rab7 transition. Going forward we will use genetic and cell biological approaches, electron microscope (EM) tomography, and biochemical reconstitution to build and test models for this critical event in organelle maturation.